Drs. Dan Drecktrah, Scott Samuels and Meghan Lybecker Awarded NIH R01
Drs. Dan Drecktrah, Scott Samuels and Meghan Lybecker were recently awarded an NIH R01. Drs. Drecktrah and Samuels are within UM's Division of Biological Sciences, while Dr. Lybecker is in the Department of Biology at the University of Colorado - Colorado Springs. Dr. Lybecker earned her PhD at the University of Montana in 2007. Drecktrah, Samuels and Lybecker will be investigating the “Regulation of glycerol utilization in Borrelia burgdorferi.” Lyme disease, the most prevalent vector-borne illness in the United States with an estimated 300,000 cases annually, is caused by infection with the spirochete Borrelia burgdorferi. B. burgdorferi is maintained in nature by cycling back and forth between a tick and a vertebrate. The spirochete shifts its source of energy from the sugar glucose in the vertebrate to the sugar alcohol glycerol in the tick: utilization of glycerol is a crucial adaptation for the spirochete to persist in the tick and successfully transmit to a vertebrate. They hypothesize that the interface of glycerol metabolism and glycolysis, the breakdown of glucose and other sugars to provide energy, is the metabolic linchpin for navigating the enzootic cycle. The central hypothesis of their grant is that B. burgdorferi uses a novel RNA-based mechanism to regulate the genes required for glycerol metabolism (glp operon) in order to survive in its tick vector. We endeavor to dissect the molecular mechanisms regulating expression of the glp operon, including the specific roles of a small antisense RNA and PlzA, a protein that binds the nucleotide signaling molecule cyclic-dimeric GMP. Genetic, biochemical, molecular, and transcriptomic approaches, as well as the tick-mouse model of Lyme disease, will be utilized to experimentally test these hypotheses as well as enhance the mechanistic understanding of carbohydrate metabolism and its regulation during the persistence of the Lyme disease agent in its tick vector.
The objective of this proposal is to understand the regulatory mechanisms that allow B. burgdorferi to respond and adapt to varied carbon sources in tick-to-mammal transmission and in Lyme disease pathogenesis, which will lead to improved diagnostic, prevention, and treatment strategies because glycerol and glucose utilization are critical for persistence during tick and vertebrate infection, respectively. The long-term objective is to alleviate human disease.